This purpose of this Research Career Award proposal is to outline a multidisciplinary line of investigation in the field of high-intensity therapeutic ultrasound with potential applications to gastrointestinal bleeding that will be used as a vehicle to gain additional scientific and engineering research experience in a mentored setting. The overall goal of this proposal is to develop a skill set that will enable me to become a highly competent and competitive independent scientific investigator applying engineering and scientific principles to solve clinical problems in the field of gastroenterology. In addition, a supplemental career development plan that includes additional coursework, career development seminars, and the formation of a scientific/career development supervisory committee is proposed. The overall purpose of the proposed research is to investigate the role of ultrasound-targeted vessel occlusion for the treatment of gastric varices. Although ultrasound is most commonly used for diagnostic purposes clinically, it is also capable of delivering energy to tissue for therapeutic purposes. At higher intensities, ultrasound has known bioeffects such as tissue heating and mechanical disruption due to cavitation. Initial studies have investigated the bioeffects that result from the exposure of blood vessels to HIFU, particularly in the setting of circulating ultrasound contrast agent (UCA). It has been demonstrated that pulsed HIFU in combination with microbubble contrast agent can lead to endothelial damage resulting in platelet activation and intravascular thrombus formation. Furthermore, it has been demonstrated that this method can be used to target vessel occlusion. This project proposes to translate basic ultrasound bioeffects studies into a clinically useful approach for treating gastric varices. The proposed studies will examine the ability of ultrasound-mediated vascular occlusion in achieving hemostasis in actively bleeding blood vessels. A prototype endoscopic transducer will be constructed to test the feasibility of ultrasound-mediated vessel occlusion in treating gastric varices in a large animal model. The overall hypothesis of this project is that ultrasound-mediated vascular occlusion can achieve hemostasis in actively bleeding blood vessels and occlude and obliterate a targeted segment of a blood vessel. This method can be translated to a clinically useful approach for the treatment of gastric varices with the development of an endoscopic-based ultrasound transducer